Selective dorsal column stimulation in SCS, using conditioning pulses

ABSTRACT

A system and method is described for preferentially stimulating dorsal column fibers while avoiding stimulation of dorsal root fibers. The invention applies hyperpolarizing pre-pulses and depolarizing pre-pulses to neural tissue, such as spinal cord tissue, through a lead placed over the spinal cord having the electrodes arranged on a line approximately transverse to the axis of the spine. To increase the threshold needed to stimulate dorsal root fibers, the anodal pulse given by each lateral contact of the electrodes has to be preceded by a depolarizing pre-pulse and simultaneously, the central electrode contact gives a hyperpolarizing pre-pulse, thereby reducing the stimulation threshold for the dorsal column fibers to subsequent depolarizing pulses.

BACKGROUND OF THE INVENTION

[0001] 1. Field of the Invention

[0002] This invention relates to an apparatus and method forelectrically stimulating neural tissue including, but not limited to, aspinal cord. More specifically, this invention relates to an apparatusand method for applying a precursor electrical pulse to neural tissueprior to a stimulation pulse with the first pulse “conditioning” thetissue for the application of the stimulation pulse.

[0003] 2. Description of the Prior Art

[0004] Nerve cells in the brain and the spinal cord have a variety ofshapes and sizes. A typical nerve cell has the shape shown in FIG. 1generally labeled 1. The classical parts of nerve cell 1 are the cellbody 2, the dendritic tree 3 and the axon 4 (including its terminalbranches). Nerve cells convey information to other cells at junctionscalled synapses.

[0005] An important property of the nerve cell is the electricalpotential that exists across the cell's outer membrane 5. Normally, whencell 1 is at rest, the inside 6 of cell 1 is 70-80 mV negative withrespect to the outside 7 of cell 1. As shown in FIG. 2, cell 1 haschemical pumps 8 imbedded in the cell membrane 5. Pumps 8 consume energyto move sodium ions 9 outside and potassium ions 10 into the cell 1 tomaintain the concentration gradients and therefore the electricalpotential difference across membrane 5.

[0006] The membrane 5 of the axon 4 has specific dynamic propertiesrelated to its function to transmit information. In man, like in othermammals, it contains sodium channels 11 and leakage channels 12.Membrane 5 has a voltage and time dependent sodium conductivity that isrelated to the number of open sodium channels. Channels 11 open andclose in response to changes in the potential across the membrane 5 ofthe cell 1. When the membrane 5 is in its resting state (70-80 mVnegative at the inside), only few sodium channels 11 are open. However,when the electrical potential across membrane 5 is reduced (membranedepolarization) to a value called the excitation threshold, the sodiumchannels 11 open up allowing sodium ions 9 to rush in (excitation). As aresult, the electrical potential across membrane 5 changes by almost 100mV, so that the inside 6 of the axon 4 gets positive with respect to theoutside 7.

[0007] After a short time the sodium channels 11 close again and theresting value of the membrane potential is restored by the flow of ionsthrough the leakage channels 12. This transient double reversal of thepotential across the membrane 5 is named “action potential”. The actionpotential, which is initiated at a restricted part of membrane 5, alsodepolarizes adjacent portions of the membrane 5 up to their excitationthreshold. Channels 11 in these portions begin to open, resulting in anaction potential at that portion of the membrane 5 which then affectsthe next section of membrane 5 and so on and so on. In this way theaction potential is propagated as a wave of electrical depolarizationalong the length of the axon 4 (FIG. 3).

[0008] After an action potential has been generated, there is arefractory period during which nerve cell 1 cannot generate anotheraction potential. The sodium channels 11 do not open again when themembrane 5 is depolarized shortly after its excitation. The effect ofthe refractory period is that action potentials are discrete signals.Trains of propagating action potentials transmit information within thenervous system, e.g. from sense organs in the skin to the spinal cordand the brain.

[0009] There are two categories of nerve fibers that carry sensoryinformation from remote sites to the spinal cord, small diameterafferent nerve fibers 13 and large diameter afferent nerve fibers 14.Generally speaking, the small diameter afferent nerve fibers 13 carrypain and temperature information to the spinal cord while the largediameter afferent nerve fibers 14 carry other sensory information suchas information about touch, skin pressure, joint position and vibrationto the spinal cord. As shown in FIG. 4, both the small and largediameter afferent nerve fibers 13, 14 enter the spinal cord 16 at thedorsal roots 17. Only large diameter nerve fibers 14 contribute branchesto the dorsal columns 15.

[0010] Melzack and Wall published a theory of pain which they called the“gate control theory.” (R. Melzack, P. D. Wall, Pain Mechanisms: A newtheory. Science 1965, 150:971-979) They reviewed past theories and dataon pain and stated that there seems to be a method to block pain at thespinal level. Within the dorsal horn of gray matter of the spinal cord,there is an interaction of small and large diameter afferent nervefibers 13, 14 through a proposed interneuron. When action potentials aretransmitted in the large diameter afferent nerve fibers 14, actionpotentials arriving along small diameter nerve fibers 13 (paininformation) are blocked and pain signals are not sent to the brain.Therefore, it is possible to stop pain signals of some origins byinitiating action potentials in the large diameter fibers. The type ofpain that can be blocked by such activity is called neuropathic pain.Chronic neuropathic pain often results from damage done to neurons inthe past.

[0011] Spinal Cord Stimulation (SCS) is one method to preferentiallyinduce action potentials in large diameter afferent nerve fibers 14.These fibers 14 bifurcate at their entry in the dorsal columns 15 intoan ascending and a descending branch (dorsal column fiber), each havingmany ramifications into the spinal gray matter to affect motor reflexes,pain message transmission or other functions. Only 20% of the ascendingbranches reach the brain (for conscious sensations).

[0012] Action potentials in the large diameter nerve fibers 14 areusually generated at lower stimulation voltages than action potentialsin small diameter nerve fibers 13. While the dorsal roots 17 could bestimulated to cause action potentials in the large diameter afferentnerve fibers 14, stimulation there can easily cause motor effects likemuscle cramps or even uncomfortable sensations. A preferred method is toplace electrodes near the midline of spinal cord 16 to limit stimulationof the nerve fibers in dorsal root 17.

[0013] Today, SCS systems use cylindrical leads or paddle-type leads toplace multiple electrodes in the epidural space over the dorsal columns15. Often the surgeon will spend an hour or more to position the leadsexactly, both to maximize pain relief and to minimize side effects. Oneof the current problems with SCS is the preferential stimulation ofnerve fibers in the dorsal roots (dorsal root nerve fibers) instead ofnerve fibers in the dorsal columns (dorsal column fibers) especially atmid-thoracic and low-thoracic vertebral levels. This is in part becausethe largest dorsal root fibers 14 have larger diameters than the largestnearby dorsal column fibers. Other factors contributing to the smallerstimulus needed to excite dorsal root fibers are the curved shape of thedorsal root fibers and the stepwise change in electrical conductivity ofthe surrounding medium at the entrance of a dorsal root into the spinalcord (J. J. Struijk et al., IEEE Trans Biomed Eng 1993, 40:632-639).Stimulation of fibers in one or more dorsal roots results in arestricted area of paresthesia. That is, paresthesia is felt in only afew dermatomes (body zones innervated by a given nerve). In contrast,dorsal column stimulation results in paresthesia in a large number ofdermatomes.

[0014] One approach to suppress the activation of dorsal root fibers andthereby favor dorsal column stimulation has been the application of anelectric field to the tissue where the shape of the electric field ischangeable and, as a result, where the location of the electric field inthe tissue is steerable. This technique has been described in U.S. Pat.No. 5,501,703 entitled Multichannel Apparatus For Epidural Spinal CordStimulation that issued Mar. 26, 1996 with Jan Holsheimer and JohannesJ. Struijk as inventors. As described in this patent, the electric fieldproduced by electrodes described in the patent is shaped and steered topreferentially activate dorsal column fibers instead of dorsal rootfibers. The invention is based on the principle that nerve fibers aredepolarized (and eventually excited) when a nearby electrode is at anegative potential, while the opposite (hyperpolarization) occurs nearelectrodes at a positive potential. A negative electrode is named acathode, because it attracts ions with a positive charge (cations). Apositive electrode is named an anode, because it attracts negative ions(anions).

[0015] In practice, electrodes are typically placed epidurally. Itappears that where the distance between the epidurally locatedelectrodes and the spinal cord is large, such as at the mid-thoracic andlow-thoracic levels, the method described in the '703 patent may stillnot sufficiently favor stimulation of the dorsal column fibers overdorsal root fibers in a number of patients (J. Holsheimer et al., Amer JNeuroradiol 1994, 15:951-959). The relatively large dorsal root fibersmay still generate action potentials at lower voltages than will nearbydorsal column fibers. As a result, the dorsal column fibers that aredesired to be stimulated have a lower probability to be stimulated thanthe dorsal root fibers, which are not desired to be stimulated and whichproduce the undesirable side effects noted above. Therefore, a differentor concurrent approach may be needed.

[0016] Grill and Mortimer (IEEE Eng Med Biol Mag 1995, 14:375-385) haveshown that applying an appropriate pre-pulse, sub-threshold to theproduction of an action potential, to neural tissue can make the nervefibers either more or less excitable. More particularly, when anappropriate sub-threshold depolarizing (cathodic) pre-pulse (DPP) isapplied to neural tissue in advance of a cathodic stimulation pulse, thenerve membrane 5 will be slightly depolarized, causing a reduction ofthe (small) number of open sodium channels 11 (FIG. 2). As a result, theexcitation threshold of the axon 4 will increase and a stronger stimulusis needed to evoke an action potential than without a DPP. Conversely,when an appropriate hyperpolarizing (anodic) pre-pulse (HPP) is appliedto neural tissue in advance of a cathodic stimulation pulse, the nervemembrane 5 will be hyperpolarized, causing an increase of the number ofopen sodium channels 11. As a result, the excitation threshold of theaxon 4 will decrease and a weaker stimulus is needed to initiate anaction potential than without an HPP.

[0017] The teaching of Grill and Mortimer is incorporated herein in itsentirety. HPP make nerve fibers more excitable while DPP make nervefibers less excitable. Grill and Mortimer have shown that for a 100 μscathodic pulse without HPP or DPP and having a sub-threshold amplitude,the application of an (anodic) HPP pulse prior to the previouslysub-threshold cathodic pulse can enable the identical 100 μs pulse tonow trigger an action potential. In particular, if a 400 μs HPP of 90%of the threshold amplitude for a 500 μs pulse, but opposite in sign,precedes the 100 μs pulse of sub-threshold amplitude, the 100 μs pulsewill create an action potential in the nerve fiber.

[0018] Conversely, Grill and Mortimer have shown that for a 100 μscathodic pulse without HPP or DPP and having a sufficient amplitude(supra-threshold) to trigger an action potential, the application of a(cathodic) DPP pulse prior to the previously supra-threshold cathodicpulse can cause the identical 100 μs pulse to now be sub-threshold. Inparticular, if a 400 μs DPP of 90% of threshold amplitude for a 500 μspulse and of the same sign precedes the 100 μs pulse of thresholdamplitude, the 100 μs pulse will now be sub-threshold and will notcreate an action potential in the nerve fiber.

[0019] Deurloo et al. (Proc. 2^(nd) Ann Conf Int Funct Electrostim Soc,1997, Vancouver, pp. 237-238) have recently shown that the effect of DPPcan be obtained more efficiently when using an exponentially increasingcathodic current instead of a rectangular current shape.

SUMMARY OF THE INVENTION

[0020] A system and method is described for preferentially stimulatingdorsal column fibers while avoiding stimulation of dorsal root fibers.The invention applies hyperpolarizing (anodic) pre-pulses (HPP) anddepolarizing (cathodic) pre-pulses (DPP) to neural tissue, such asspinal cord tissue, through a lead placed over the spinal cord havingthe electrodes arranged on a line approximately transverse to the axisof the spine. To increase the threshold needed to stimulate dorsal rootfibers, the anodal pulse given by each lateral contact of the electrode,is preceded by a DPP. The cathodic pulse, given simultaneously by thecentral electrode contact is preceded by an HPP, thereby reducing thestimulation threshold for the dorsal column fibers.

[0021] It is therefore a primary object of the invention to provide asystem and method for treating pain by spinal cord stimulation (SCS) bypreferentially stimulating dorsal column fibers over dorsal root fibers.

[0022] It is another primary object of the invention to provide a systemand method for electrically stimulating the spinal cord bypreferentially stimulating dorsal column fibers over dorsal root fibers.

[0023] It is another primary object of the invention to provide a systemand method for electrically and preferentially stimulating selectedregions of the brain and peripheral nerves.

[0024] It is another object of the invention to provide a system andmethod for treating pain by SCS by preferentially stimulating dorsalcolumn fibers over dorsal root fibers that is easy to use.

[0025] It is another object of the invention to provide a system andmethod for electrically stimulating the spinal cord by preferentiallystimulating dorsal column fibers over dorsal root fibers that is easy touse.

[0026] These and other objects of the invention will be clear to thoseskilled in the art from the description contained herein and moreparticularly with reference to the Drawings and the Detailed Descriptionof the Invention where like elements, wherever referenced, are referredto by like reference numbers.

BRIEF DESCRIPTION OF THE DRAWINGS

[0027]FIG. 1 is a schematic view of a nerve cell.

[0028]FIG. 2 is a schematic view of the chemical pumps and voltagedependent channels in the membrane of the nerve cell of FIG. 1.

[0029]FIG. 3 is a schematic view of the nerve cell of FIG. 1 showing thepropagation of an action potential.

[0030]FIG. 4 is a cross-sectional view of the spine.

[0031]FIG. 5 is a schematic view of the present invention.

[0032]FIG. 6 is a graphic representation of the signals applied to theelectrodes of the preferred embodiment of the present invention.

DETAILED DESCRIPTION OF THE INVENTION

[0033] A system of the present invention is shown in FIG. 5 generallylabeled 10. System 10 includes an electric signal generator that ispreferably an implantable electric pulse generator (IPG) 12. IPG 12preferably is a device having at least two channels that may beindependently controllable in amplitude, frequency, timing and pulsewidth. In the preferred embodiment, IPG 12 has two such channels.

[0034] The pulse generator may also be a pulse generator that isconnected to an implanted receiver that receives power and programmingfrom an external transmitter by RF coupling. Such a system could be aMatrix® radio-frequency pulse generator available from Medtronic, Inc.of Minneapolis, Minn.

[0035] Alternately, an IPG 12 with three independently controllablechannels can be used. In another alternate embodiment, IPG 12 may have asingle channel. Such a system could be an Itrel® implantable pulsegenerator available from Medtronic, Inc. of Minneapolis, Minn. It isalso to be understood that IPG 12 may be any device providing electricalsignals whether or not those signals are electrical pulses. For example,IPG 12 may, instead of providing electrical pulses, provide electricalsignals of varying amplitude and frequency such as sinusoidal waves orother relatively continuous signals.

[0036] IPG 12 is electrically connected to a lead 14 for applyingstimulation pulses. Lead 14 has a series of electrodes 16 a,b,c arrangedon a line 20 on a paddle 18. In the preferred embodiment, electrodes 16are located along line 20 so that when lead 14 is implanted in a patientalong a patient's spinal cord, line 20 is transverse to the axis of thespinal cord. In an alternate embodiment, electrodes 16 a,b,c are locatedalong a line 20′ that is parallel to the axis of the spinal cord. Ineither embodiment, electrode 16 b is located between electrodes 16 a and16 c.

[0037] In the embodiment where IPG 12 has one channel, electrodes 16 a,care attached to one output of IPG 12, while electrode 16 b is connectedto the other output. In the embodiment where IPG 12 has two or morechannels, electrode 16 b is attached to the output the channels have incommon, while each electrode 16 a,c is attached to the non-common outputof a different channel.

[0038] In operation, lead 14 is implanted epidurally by techniques wellknown to those in the art and advanced to a desired location along thepatient's spinal column. In this position, with the preferred embodimentof lead 14, line 20 containing electrodes 16 a,b and c is locatedtransverse to the axis of the spinal cord.

[0039] With lead 14 in place and connected to IPG 12, a pulse patternaccording to the present invention is applied to electrodes 16 as willbe described hereafter. This pulse pattern will produce the desiredobjective of preferentially stimulating the dorsal column fibers whileinhibiting the stimulation of the dorsal root fibers.

[0040] The pulse pattern presented to electrodes 16 is shown in FIG. 6.The pulse pattern presented to electrodes 16 a,c is labeled “A”. Thesimultaneous pulse pattern of opposite sign presented to electrode 16 bis labeled “B”.

[0041] Pulse pattern “A” has two parts, a depolarizing (cathodic)pre-pulse (DPP) labeled A1 followed by an anodic pulse A2. The DPP A1should desensitize membranes of the neural tissue to be affected by thestimulation pulse A2. Experience has shown that an effective DPP A1 isabout 500 μs long and has an amplitude of about 90% of the thresholdamplitude for a 500 μs pulse. The DPP A1 should be opposite in sign tothe stimulation pulse A2 as will be described hereafter. Although aspecific DPP A1 has been described, any DPP shape that results indesensitization of the membranes of neural tissue being stimulated maybe used and is within the scope of the invention.

[0042] Immediately after the pre-pulse A1, an anodic stimulation pulseA2 is applied. Stimulation pulse A2 has sufficient amplitude andduration to greatly inhibit the production of action potentials inneural tissue near electrodes 16 a,c. The operation of such astimulation pulse through the configuration of lead 14 may preferablyapply a concept known as “transverse tripolar stimulation” that isexplained in detail in U.S. Pat. No. 5,501,703 issued to Jan Holsheimerand Johannes J. Struijk on Mar. 26, 1996 entitled “MultichannelApparatus for Epidural Spinal Cord Stimulator”, the teachings of whichare incorporated by reference in its entirety.

[0043] Pulse pattern “B” also has two parts, an anodic hyperpolarizingpre-pulse (HPP) B1 followed by a cathodic pulse B2. The HPP B1 shouldsensitize the cell membranes of the neural tissue to be affected by thestimulation pulse B2. Because all current flows between electrode 16 band electrodes 16 a,c, the current of pulse B1 is identical to the sumof the currents of pulses A1 at electrodes 16 a and 16 c andsimultaneous. Likewise, the current of pulse B2 is identical to the sumof the currents of A2 at electrodes 16 a and 16 c and simultaneous. Inaddition, pulses A1 and A2 should be opposite in sign to pulses B1 andB2, respectively. Because DPP A1 is about 500 μs long, HPP B1 is alsoabout 500 μs long. Although a specific HPP B1 has been described, anyHPP shape that results in sensitization of the membranes of neuraltissue being stimulated may be used and is within the scope of theinvention. Immediately after the HPP B1, a cathodic pulse B2 is applied.Pulse B2 has sufficient amplitude and duration to generate actionpotentials in neural tissue near electrode 16 b.

[0044] To avoid “anodal break excitation”, the duration and themagnitude of the hyperpolarizing pulse A2 might have to be limited toavoid activation of nerve cells at the end of this pulse. Alternately,the trailing edge of the pulse might need to be ramped down (c.f., Z. P.Fang and J. T. Mortimer, IEEE Trans Biomed Eng 1991, 38:168-174; G. S.Brindley, M. D. Craggs, JNeurol Neurosurg Psychiatry 1980,43:1083-1090).

[0045] In the preferred embodiment electrode 16 b is placed generallyover the center of the spinal cord, and consequently near the dorsalcolumns 15, but away from the left and right dorsal roots 17. The HPP B1will cause the dorsal column fibers closest to electrode 16 b to behyperpolarized and therefore more susceptible to the subsequentstimulation pulse B2. Conversely, electrodes 16 a and 16 c are locatednear the nerve fibers in the dorsal roots 17. The DPP A1 will cause thenerve fibers in the dorsal roots 17 to be slightly depolarized andtherefore less likely to respond to the stimulation pulse A2. As aresult, stimulation of dorsal root fibers can be avoided at a higheramplitude of the stimulation pulse A2 with a DPP A1 than it could bewithout a DPP A1.

[0046] As can be seen in FIG. 6, in the embodiment of IPG 12 with asingle channel, pre-pulses A1 and B1 are equal in time as are anodicpulse A2 and cathodic pulse B2. In the embodiment having separatechannels of IPG 12 connected to 16 a-b and 16 b-c, stimulation pulses A2and B2 may have different amplitudes for contacts 16 a-b and 16 b-c.However, these pulses should largely overlap in time to create anelectrical field promoting the stimulation of dorsal column fibers andthe inhibition of dorsal root fibers, according to the concept known as“transverse tripolar stimulation” and described in U.S. Pat. No.5,501,703 and in a paper (Med Biol Eng Comp 1996, 34:273-279). Likewise,pre-pulses A1 and B1 should largely overlap in time to promote thesensitization of dorsal column fibers and desensitization of dorsal rootfibers. When a third channel of IPG 12 is available, this channel can beconnected to a contact 16 a,b,c and to the metal casing of the IPG. Foreither case, for every stimulation pulse the invention anticipates theapplication of pre-pulses.

[0047] It is believed to be important to have a zero net charge to andfrom electrodes 16 a,b,c for each stimulation pulse. This minimizeselectrode degradation and cell trauma. Ordinarily, a zero net charge isaccomplished by applying a charge-balancing pulse to an electrode,opposite in sign and immediately after a stimulation pulse applied tothe same electrode. The charge-balancing pulse has an amplitude andduration compensating for the charge injected by the stimulation pulse.This is usually accomplished by a charge-balancing pulse having a longduration and a low amplitude.

[0048] The application of cathodic and anodic pre-pulses A1 and B1 makesit easier to achieve this zero net charge, because these pre-pulses areopposite in sign to pulses A2 and B2, respectively. Therefore, theapplication of a pre-pulse makes the charge-balancing pulse smaller. Ifpre-pulses A1 and B1 are chosen correctly, the charge-balancing pulsesmay be eliminated altogether.

[0049] The application of HPP and DPP has been described in connectionwith stimulation of neural tissue in the spinal cord. The principal ofthe invention can be applied to neural tissue generally where it isdesired to shield certain cells from the effects of nearby cathodalstimulation. For example, it may be desirable to preferentiallystimulate certain brain cells while avoiding stimulating other nearbybrain cells.

[0050] In one embodiment, a lead 14 having a first electrode 16 a and asecond electrode 16 b would be inserted in the brain and moved to thedesired location with electrode 16 b near the area to be preferentiallystimulated and electrode 16 a moved near an area that it is desirablenot to stimulate or to inhibit. A hyperpolarizing pre-pulse B1 may beapplied to electrode 16 b and a depolarizing pre-pulse A1 applied toelectrode 16 a. These pulses may both be applied or may be applied inthe alternative, that is, either a hyperpolarizing pre-pulse B1 or adepolarizing pre-pulse A1 may be applied to electrode 16 b.

[0051] In a variant of this embodiment, a lead 14 having two outsideelectrodes 16 a,c and a center electrode 16 b would be inserted in thebrain and moved to the desired location with electrode 16 b near thearea to be preferentially stimulated and electrodes 16 a,c moved nearthe areas that it is desirable not to stimulate or to inhibit. Ahyperpolarizing pre-pulse B1 may be applied to electrode 16 b and adepolarizing pre-pulse A1 applied to electrodes 16 a,c. These pulses mayboth be applied or may be applied in the alternative.

[0052] In a variant of this embodiment, as before, a lead 14 having twooutside electrodes 16 a,c and a center electrode 16 b would be insertedin the brain and moved to the desired location. In this variant,electrode 16 b is placed near the area to be preferentially inhibitedwhile electrodes 16 a,c are moved near the areas that it is desirable tostimulate. A depolarizing pre-pulse A1 is sent to electrode 16 b while ahyperpolarizing pre-pulse B1 is sent to electrodes 16 a,c.

[0053] In another embodiment, a lead 14 having two outside electrodes 16a,c and a center electrode 16 b would be placed on or near the surfaceof the brain, for example, on the cortex, and moved to the desiredlocation with electrode 16 b near the area to be preferentiallystimulated and electrodes 16 a,c moved near the areas that it isdesirable not to stimulate or to inhibit. The lead is then operated asdescribed above in connection with stimulating spinal cord tissue. Inthis embodiment, the lead may be placed either sub-durally orepidurally.

[0054] In any of the embodiments of the lead having three electrodes,whether for use on the spine, in the brain or on peripheral nerve, theelectrodes may be arranged along a single line or may be arranged in atwo or three-dimensional array, that is, so that only two electrodes areon a single line.

[0055] Likewise, it may be desirable to preferentially stimulate certainnerve fibers in a peripheral nerve or spinal nerve root while avoidingstimulating other nearby nerve fibers. In one embodiment, a lead 14having two outside electrodes 16 a,c and a center electrode 16 b wouldbe placed around part of a nerve bundle so that line 20 is transverse tothe axis of the nerve bundle and electrode 16 b is near the nerve fibersto be preferentially stimulated. The lead is then operated as describedabove in connection with stimulating spinal cord tissue.

[0056] In another embodiment, a number of electrodes are placed at theinside of a nerve cuff, transverse to the axis of the nerve bundle. Oneelectrode near the nerve fibers to be preferentially stimulated isselected as the electrode 16 b, while the neighboring ones are selectedas electrodes 16 a,c. The lead is then operated as described above inconnection with stimulating spinal cord tissue.

[0057] While this invention has been described with reference toillustrative embodiments, this description is not intended to beconstructed in a limiting sense. Various modifications of theillustrative embodiments, as well as other embodiments of the invention,will be apparent to persons skilled in the art upon reference to thisdescription. It is therefore contemplated that the appended claims willcover any such modifications or embodiments as fall within the truescope of the invention.

We claim:
 1. A method of electrically stimulating neural tissue of thespinal cord comprising the steps of: providing a source of electricalpulses; providing a first electrode and an electrical return path;connecting the first electrode to the source of electrical pulses;placing the first electrode near a patient's spinal cord; applying ahyperpolarizing electrical pre-pulse to the tissue through the firstelectrode and source of electrical pulses whereby the tissue is moresusceptible to subsequent electric stimulation.
 2. The method of claim 1further comprising the step of applying a subsequent depolarizingelectrical pulse to the tissue through the first electrode.
 3. Themethod of claim 1 wherein the step of providing an electrical returnpath includes the step of providing an electrical return path thatincludes a second electrode.
 4. The method of claim 1 wherein the stepof providing an electrical return path includes the step of providing anelectrical return path that includes the source of electrical pulses. 5.The method of claim 1 wherein the step of placing the first electrodenear a patient's spinal cord includes the step of placing the firstelectrode near a patient's spinal cord so that the first electrode isgenerally over a midline of the patient's spinal cord.
 6. The method ofclaim 1 wherein the step of placing the first electrode includes thestep of implanting the first electrode within the patient's body near apatient's spinal cord.
 7. The method of claim 1 wherein the step ofproviding the first electrode includes the step of providing a secondelectrode spaced from the first electrode and further comprising thestep of connecting the second electrode to the source of electricalpulses.
 8. The method of claim 7 further comprising the step of:applying a depolarizing electrical pre-pulse to the tissue through thesecond electrode and source of electrical pulses whereby the tissue nearthe second electrode is less susceptible to subsequent electricstimulation.
 9. The method of claim 8 wherein the step of placing thefirst electrode near a patient's spinal cord includes the step ofplacing the second electrode near a dorsal root of the patient's spinalcord.
 10. The method of claim 8 wherein the step of providing a firstelectrode and a second electrode spaced from the first electrodeincludes the step of providing a third electrode spaced from the firstelectrode opposite the second electrode so that the first electrode isgenerally between the second and third electrodes and further comprisingthe step of connecting the third electrode to the source of electricalpulses.
 11. The method of claim 10 further comprising the step of:applying a depolarizing electrical pre-pulse to the tissue through thethird electrode and source of electrical pulses whereby the tissue nearthe third electrode is less susceptible to subsequent electricstimulation.
 12. The method of claim 1 wherein the step of placing thefirst electrode near a patient's spinal cord includes the step ofplacing the third electrode near a dorsal root of the patient's spinalcord wherein the dorsal root near the third electrode is different thanthe dorsal root near the second electrode.
 13. The method of claim 7wherein the step of providing a first electrode and a second electrodespaced from the first electrode includes the step of providing a thirdelectrode spaced from the first electrode opposite the second electrodeso that the first electrode is generally between the second and thirdelectrodes and further comprising the step of connecting the thirdelectrode to the source of electrical pulses.
 14. The method of claim 13further comprising the step of: applying a depolarizing electricalpre-pulse to the tissue through the third electrode and source ofelectrical pulses whereby the tissue near the third electrode is lesssusceptible to subsequent electric stimulation.
 15. The method of claim14 wherein the step of placing the first electrode near a patient'sspinal cord includes the step of placing the third electrode near adorsal root of the patient's spinal cord wherein the dorsal root nearthe third electrode is different than the dorsal root near the secondelectrode.
 16. The method of claim 13 wherein the step of providing afirst, second and third electrode includes the step of providing afirst, second and third electrode on a single lead.
 17. The method ofclaim 7 wherein the step of providing a first and second electrodeincludes the step of providing a first and second electrode on a singlelead.
 18. The method of claim 1 further comprising the step ofimplanting the source of electrical pulses within the patient's body.19. A method of electrically stimulating neural tissue of the spinalcord comprising the steps of: providing a source of electrical pulseshaving a first and a second output; providing a lead having a firstelectrode and a second electrode spaced from the first electrode;connecting the lead to the source of electrical pulses so that the firstand second electrodes are connected to the first and second outputs,respectively, of the source of electrical pulses; placing the leadwithin a patient's body near a patient's spinal cord so that the firstelectrode is generally over a midline of the patient's spinal cord;applying a hyperpolarizing electrical pre-pulse to the tissue throughthe first electrode of the lead and source of electrical pulses wherebythe tissue is more susceptible to subsequent electric stimulation;applying a depolarizing electrical pre-pulse to the tissue through thesecond electrode of the lead and source of electrical pulses whereby thetissue near the second electrode is less susceptible to subsequentelectric stimulation.
 20. The method of claim 19 further comprising thestep of applying a subsequent depolarizing electrical pulse to thetissue through the first electrode.
 21. The method of claim 19 furthercomprising the step of applying a subsequent hyperpolarizing electricalpulse to the tissue through the second electrode.
 22. The method ofclaim 19 wherein the step of placing the lead near a patient's spinalcord includes the step of placing the second electrode near a dorsalroot of the patient's spinal cord.
 23. The method of claim 19 whereinthe step of providing a lead having a first electrode and a secondelectrode spaced from the first electrode includes the step of providinga third electrode spaced from the first electrode opposite the secondelectrode so that the first electrode is generally between the secondand third electrodes and wherein the step of connecting the lead to thesource of electrical pulses also includes the step of connecting thethird electrode to the second output of the source of electrical pulses.24. The method of claim 23 further comprising the step of: applying adepolarizing electrical pre-pulse to the tissue through the thirdelectrode of the lead and source of electrical pulses whereby the tissuenear the third electrode is less susceptible to subsequent electricstimulation; and, applying a subsequent hyperpolarizing electrical pulseto the tissue through the third electrode.
 25. The method of claim 24wherein the step of placing the lead near a patient's spinal cordincludes the step of placing the third electrode near a dorsal root ofthe patient's spinal cord wherein the dorsal root near the thirdelectrode is different than the dorsal root near the second electrode.26. The method of claim 19 further comprising the step of implanting thesource of electrical pulses within the patient's body.
 27. A method ofelectrically stimulating neural tissue of the spinal cord comprising thesteps of: providing a source of electrical pulses having a first and asecond output; providing a lead having a first electrode, a secondelectrode spaced from the first electrode and a third electrode spacedfrom the first electrode opposite the second electrode so that the firstelectrode is generally between the second and third electrodes;connecting the lead to the source of electrical pulses so that the firstelectrode is connected to the first output of the source of electricalpulses and the second and third electrodes are connected to the secondoutput of the source of electrical pulses; placing the lead within apatient's body near a patient's spinal cord so that the first electrodeis generally over a midline of the patient's spinal cord and so that thesecond and third electrodes are near different dorsal roots of thepatient's spinal cord; applying a hyperpolarizing electrical pre-pulseto the tissue through the first electrode of the lead and source ofelectrical pulses whereby the tissue is more susceptible to subsequentelectric stimulation; applying a depolarizing electrical pre-pulse tothe tissue through the second and third electrodes of the lead andsource of electrical pulses whereby the tissue near the second and thirdelectrodes is less susceptible to subsequent electric stimulation. 28.The method of claim 27 further comprising the step of applying asubsequent depolarizing electrical pulse to the tissue through the firstelectrode.
 29. The method of claim 27 further comprising the step ofapplying a subsequent hyperpolarizing electrical pulse to the tissuethrough the second and third electrodes.
 30. The method of claim 27further comprising the step of implanting the source of electricalpulses within the patient's body.
 31. A method of electricallystimulating neural tissue of the spinal cord comprising the steps of:providing a source of electrical pulses; providing a first electrode andan electrical return path; connecting the first electrode to the sourceof electrical pulses; placing the first electrode near a patient'sspinal cord; applying a depolarizing electrical pre-pulse to the tissuethrough the first electrode and source of electrical pulses whereby thetissue is less susceptible to subsequent electric stimulation; applyinga subsequent hyperpolarizing electrical pulse to the tissue through thefirst electrode.
 32. The method of claim 31 wherein the step ofproviding an electrical return path includes the step of providing anelectrical return path that includes a second electrode.
 33. The methodof claim 31 wherein the step of providing an electrical return pathincludes the step of providing an electrical return path that includesthe source of electrical pulses.
 34. The method of claim 31 wherein thestep of placing the first electrode near a patient's spinal cordincludes the step of placing the first electrode near a patient's spinalcord so that the first electrode is generally over a dorsal root of thepatient's spinal cord.
 35. The method of claim 31 wherein the step ofplacing the first electrode includes the step of implanting the firstelectrode within the patient's body near a patient's spinal cord. 36.The method of claim 31 wherein the step of providing a first electrodeincludes providing a second electrode spaced from the first electrodeand further comprising the step of connecting the second electrode tothe source of electrical pulses.
 37. The method of claim 36 furthercomprising the step of: applying a depolarizing electrical pre-pulse tothe tissue through the second electrode and source of electrical pulseswhereby the tissue near the second electrode is less susceptible tosubsequent electric stimulation.
 38. The method of claim 37 wherein thestep of placing the first electrode near a patient's spinal cordincludes the step of placing the second electrode near a dorsal root ofthe patient's spinal cord.
 39. The method of claim 38 wherein the stepof providing a first electrode and a second electrode spaced from thefirst electrode includes the step of providing a third electrode spacedfrom the first electrode opposite the second electrode so that the firstelectrode is generally between the second and third electrodes andfurther comprising the step of connecting the third electrode to thesource of electrical pulses.
 40. The method of claim 39 furthercomprising the step of: applying a depolarizing electrical pre-pulse tothe tissue through the third electrode and source of electrical pulseswhereby the tissue near the third electrode is less susceptible tosubsequent electric stimulation.
 41. The method of claim 40 wherein thestep of placing the first electrode near a patient's spinal cordincludes the step of placing the third electrode near a dorsal root ofthe patient's spinal cord.
 42. The method of claim 37 wherein the stepof placing the first electrode near a patient's spinal cord includes thestep of placing the first electrode near a patient's spinal cord so thatthe first electrode is generally over a first dorsal root of thepatient's spinal cord and so that the second electrode is placed near asecond dorsal root of the patient's spinal cord wherein the first dorsalroot is different than the second dorsal root.
 43. The method of claim36 wherein the step of providing a first electrode and a secondelectrode spaced from the first electrode includes the step of providinga third electrode spaced from the first electrode opposite the secondelectrode so that the first electrode is generally between the secondand third electrodes and further comprising the step of connecting thethird electrode to the source of electrical pulses.
 44. The method ofclaim 31 further comprising the step of implanting the source ofelectrical pulses within the patient's body.
 45. A method ofelectrically stimulating neural tissue of the brain comprising the stepsof: providing a source of electrical pulses; providing a firstelectrode; providing an electrical return path; connecting the firstelectrode to the source of electrical pulses; placing the firstelectrode in tissue of a patient's brain; applying a hyperpolarizingelectrical pre-pulse to the tissue through the first electrode andsource of electrical pulses whereby the tissue is more susceptible tosubsequent electric stimulation.
 46. The method of claim 45 furthercomprising the step of applying a subsequent depolarizing electricalpulse to the tissue through the first electrode.
 47. The method of claim45 wherein the step of providing an electrical return path includes thestep of providing an electrical return path that includes a secondelectrode.
 48. The method of claim 45 wherein the step of providing anelectrical return path includes the step of providing an electricalreturn path that includes the source of electrical pulses.
 49. Themethod of claim 45 wherein the step of providing a first electrodehaving a first electrode includes providing a second electrode spacedfrom the first electrode and further comprising the step of connectingthe second electrode to the source of electrical pulses.
 50. The methodof claim 49 further comprising the step of: applying a depolarizingelectrical pre-pulse to the tissue through the second electrode andsource of electrical pulses whereby the tissue near the second electrodeis less susceptible to subsequent electric stimulation.
 51. The methodof claim 50 wherein the step of providing a first electrode and a secondelectrode spaced from the first electrode includes the step of providinga third electrode spaced from the first and second electrodes andfurther comprising the step of connecting the third electrode to thesource of electrical pulses.
 52. The method of claim 51 furthercomprising the step of: applying a depolarizing electrical pre-pulse tothe tissue through the third electrode and source of electrical pulseswhereby the tissue near the third electrode is less susceptible tosubsequent electric stimulation.
 53. The method of claim 51 furthercomprising the step of: applying a hyperpolarizing electrical pre-pulseto the tissue through the third electrode and source of electricalpulses whereby the tissue near the third electrode is more susceptibleto subsequent electric stimulation.
 54. The method of claim 45 furthercomprising the step of implanting the source of electrical pulses withinthe patient's body.
 55. A method of electrically stimulating neuraltissue of the brain comprising the steps of: providing a source ofelectrical pulses; providing a first electrode; providing an electricalreturn path; connecting the first electrode to the source of electricalpulses; placing the first electrode in tissue of a patient's brain;applying a depolarizing electrical pre-pulse to the tissue through thefirst electrode and source of electrical pulses whereby the tissue isless susceptible to subsequent electric stimulation.
 56. The method ofclaim 55 further comprising the step of applying a subsequenthyperpolarizing electrical pulse to the tissue through the firstelectrode.
 57. A method of electrically stimulating neural tissue of thebrain comprising the steps of: providing a source of electrical pulses;providing a first electrode; providing an electrical return path;connecting the first electrode to the source of electrical pulses;placing the first electrode on the surface of a patient's brain;applying a hyperpolarizing electrical pre-pulse to the tissue throughthe first electrode and source of electrical pulses whereby the tissueis more susceptible to subsequent electric stimulation; applying asubsequent depolarizing electrical pulse to the tissue through the firstelectrode.
 58. The method of claim 57 wherein the step of providing anelectrical return path includes the step of providing an electricalreturn path that includes a second electrode.
 59. The method of claim 57wherein the step of providing an electrical return path includes thestep of providing an electrical return path that includes the source ofelectrical pulses.
 60. The method of claim 57 wherein the step ofproviding a first electrode includes the step of providing a secondelectrode spaced from the first electrode and further comprising thestep of connecting the second electrode to the source of electricalpulses.
 61. The method of claim 60 further comprising the step of:applying a depolarizing electrical pre-pulse to the tissue through thesecond electrode and source of electrical pulses whereby the tissue nearthe second electrode is less susceptible to subsequent electricstimulation.
 62. The method of claim 61 wherein the step of providing afirst electrode and a second electrode spaced from the first electrodeincludes the step of providing a third electrode spaced from the firstand second electrodes and further comprising the step of connecting thethird electrode to the source of electrical pulses.
 63. The method ofclaim 62 further comprising the step of: applying a depolarizingelectrical pre-pulse to the tissue through the third electrode andsource of electrical pulses whereby the tissue near the third electrodeis less susceptible to subsequent electric stimulation.
 64. The methodof claim 62 further comprising the step of: applying a hyperpolarizingelectrical pre-pulse to the tissue through the third electrode andsource of electrical pulses whereby the tissue near the third electrodeis more susceptible to subsequent electric stimulation.
 65. The methodof claim 57 further comprising the step of implanting the source ofelectrical pulses within the patient's body.
 66. A method ofelectrically stimulating neural tissue of the brain comprising the stepsof: providing a source of electrical pulses; providing a firstelectrode; providing an electrical return path; connecting the firstelectrode to the source of electrical pulses; placing the firstelectrode on the surface of a patient's brain; applying a depolarizingelectrical pre-pulse to the tissue through the first electrode andsource of electrical pulses whereby the tissue is less susceptible tosubsequent electric stimulation.
 67. The method of claim 66 furthercomprising the step of applying a subsequent hyperpolarizing electricalpulse to the tissue through the first electrode.
 68. A method ofelectrically stimulating neural tissue of the brain comprising the stepsof: providing a source of electrical pulses; providing a firstelectrode, a second electrode spaced from the first electrode and athird electrode spaced from the first electrode opposite the secondelectrode so that the first electrode is generally between the secondand third electrodes; providing an electrical return path; connectingthe first, second and third electrodes to the source of electricalpulses; placing the first, second and third electrodes within apatient's body in a patient's brain; applying a hyperpolarizingelectrical pre-pulse to the tissue through the first electrode andsource of electrical pulses whereby the tissue is more susceptible tosubsequent electric stimulation; applying a depolarizing electricalpre-pulse to the tissue through the second and third electrodes andsource of electrical pulses whereby the tissue near the second and thirdelectrodes is less susceptible to subsequent electric stimulation. 69.The method of claim 68 further comprising the step of applying asubsequent depolarizing electrical pulse to the tissue through the firstelectrode.
 70. The method of claim 68 further comprising the step ofimplanting the source of electrical pulses within the patient's body.71. A method of electrically stimulating peripheral nerve neural tissue,the peripheral nerve tissue having an axis generally aligned with theelongated dimension of the tissue, the method comprising the steps of:providing a source of electrical pulses; providing a first electrode anda second electrode, the first and second electrodes located along aline; providing an electrical return path; connecting the first andsecond electrodes to the source of electrical pulses; placing the firstelectrode near a patient's peripheral nerve so that the line includingthe first and second electrodes is generally transverse to the axis ofthe peripheral nerve; applying a hyperpolarizing electrical pre-pulse tothe tissue through the first electrode and source of electrical pulseswhereby the tissue is more susceptible to subsequent electricstimulation; applying a depolarizing electrical pre-pulse to the tissuethrough the second electrode and source of electrical pulses whereby thetissue near the second electrode is less susceptible to subsequentelectric stimulation; applying a subsequent depolarizing electricalpulse to the tissue through the first electrode.
 72. The method of claim71 wherein the step of providing an electrical return path includes thestep of providing an electrical return path that includes the source ofelectrical pulses.
 73. The method of claim 71 wherein the step ofproviding a first electrode and a second electrode includes the step ofproviding a third electrode and further comprising the step ofconnecting the third electrode to the source of electrical pulses. 74.The method of claim 73 wherein the step of providing a third electrodeincludes the step of providing a third electrode located generally alongthe line containing the first and second electrodes on the side of thefirst electrode opposite the second electrode.
 75. The method of claim74 wherein the step of applying a depolarizing electrical pre-pulse tothe tissue through the second electrode and source of electrical pulsesalso includes the step of applying a depolarizing electrical pre-pulseto the tissue through the third electrode and source of electricalpulses whereby the tissue near the third electrode is less susceptibleto subsequent electric stimulation.
 76. The method of claim 74 whereinthe step of applying a depolarizing electrical pre-pulse to the tissuethrough the second electrode and source of electrical pulses alsoincludes the step of applying a hyperpolarizing electrical pre-pulse tothe tissue through the third electrode and source of electrical pulseswhereby the tissue near the third electrode is more susceptible tosubsequent electric stimulation.
 77. The method of claim 73 wherein thestep of applying a depolarizing electrical pre-pulse to the tissuethrough the second electrode and source of electrical pulses alsoincludes the step of applying a depolarizing electrical pre-pulse to thetissue through the third electrode and source of electrical pulseswhereby the tissue near the third electrode is less susceptible tosubsequent electric stimulation.
 78. The method of claim 73 wherein thestep of applying a depolarizing electrical pre-pulse to the tissuethrough the second electrode and source of electrical pulses alsoincludes the step of applying a hyperpolarizing electrical pre-pulse tothe tissue through the third electrode and source of electrical pulseswhereby the tissue near the third electrode is more susceptible tosubsequent electric stimulation.
 79. A method of electricallystimulating peripheral nerve neural tissue comprising the steps of:providing a source of electrical pulses; providing a first electrode, asecond electrode and a third electrode located on the side of the firstelectrode opposite the second electrode, the first, second and thirdelectrodes located generally along a line; providing an electricalreturn path; connecting the first, second and third electrodes to thesource of electrical pulses; placing the first, second and thirdelectrodes near a patient's peripheral nerve so that the line includingthe first, second and third electrodes is generally transverse to theaxis of the peripheral nerve; applying a depolarizing electricalpre-pulse to the tissue through the first electrode and source ofelectrical pulses whereby the tissue is less susceptible to subsequentelectric stimulation; applying a hyperpolarizing electrical pre-pulse tothe tissue through the second electrode and source of electrical pulseswhereby the tissue near the second electrode is more susceptible tosubsequent electric stimulation. 80 The method of claim 79 furthercomprising the step of applying a subsequent depolarizing electricalpulse to the tissue through the second electrode.
 81. The method ofclaim 79 further comprising the step of applying a hyperpolarizingelectrical pre-pulse to the tissue through the third electrode andsource of electrical pulses whereby the tissue near the third electrodeis more susceptible to subsequent electrical stimulation. 82 The methodof claim 81 further comprising the step of applying a subsequentdepolarizing electrical pulse to the tissue through the third electrode.83. The method of claim further comprising the step of applying adepolarizing electrical pre-pulse to the tissue through the thirdelectrode and source of electrical pulses whereby the tissue near thethird electrode is less susceptible to subsequent electricalstimulation.